McVeigh, T.P., Monahan, K.J., Christopher, J. et al. (86 more authors) (2024) Extent of investigation and management of cases of ‘unexplained’ mismatch repair deficiency (u-dMMR): a UK Cancer Genetics Group consensus. Journal of Medical Genetics, 61 (7). pp. 707-715. ISSN 0022-2593
Abstract
Background Mismatch repair deficiency (dMMR) is a characteristic feature of cancers linked to Lynch syndrome. However, in most cases, it results from sporadic somatic events rather than hereditary factors. The term'Lynch-like syndrome' (LLS) has been used to guide colorectal cancer surveillance for relatives of individuals with a dMMR tumour when somatic and germline genomic testing is uninformative. As the assessment of mismatch repair through immunohistochemistry and/or microsatellite instability is increasingly applied across various tumour types for treatment planning, dMMR is increasingly detected in tumours where suspicion of hereditary aetiology is low. Our objective was to establish current practices and develop national guidance for investigating, and managing relatives of, patients with cancers demonstrating unexplained dMMR. Methods This was achieved through a virtual consensus meeting involving key stakeholders from the UK, through premeeting surveys, structured discussions and in-meeting polling to formulate best practice guidance. Results We identified variability in the availability of diagnostic technologies across specialist centres. It was agreed that equitable access to baseline testing is required, acknowledging the need for a pragmatic approach to investigating dMMR cancers not traditionally associated with Lynch syndrome. Factors such as family history, age, tumour type, protein loss pattern and extent of the investigation were deemed crucial in guiding family management. The term'unexplained dMMR' was recommended over LLS. Conclusion Decisions regarding investigations and future cancer risk management in patients and relatives should be nuanced, considering factors like clinical suspicion of hereditary predisposition to allocate limited resources efficiently and avoid unnecessary investigations in low-suspicion families.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. |
Keywords: | 32 Biomedical and Clinical Sciences; 3211 Oncology and Carcinogenesis; Rare Diseases; Clinical Research; Cancer; Genetics; Colo-Rectal Cancer; Digestive Diseases; 7.1 Individual care needs; Cancer; Humans; United Kingdom; DNA Mismatch Repair; Colorectal Neoplasms, Hereditary Nonpolyposis; Consensus; Colorectal Neoplasms; Microsatellite Instability; Genetic Testing; Neoplastic Syndromes, Hereditary; Genetic Predisposition to Disease; Brain Neoplasms |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Pathology and Data Analytics |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Aug 2024 15:49 |
Last Modified: | 07 Aug 2024 15:49 |
Published Version: | http://dx.doi.org/10.1136/jmg-2024-109886 |
Status: | Published |
Publisher: | BMJ |
Identification Number: | 10.1136/jmg-2024-109886 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215846 |